inflammatory bowel disease

Question 1

who most susceptible to crohs/ulcerative colitis

Answer 1

white europeans

Question 2

environmental risk factors of IBD

Answer 2

smoking, diet, and drugs, all of which may impact microbiome

Question 3

what is IBD

Answer 3

autoimmune disease, where there is disruption between gut microbes and host cells, leading to inflammation

Question 4

crohns vs UC- cytokines involves, apoptosis, layers and part of GI, patchy or continuous, fistulae or not, and effect of surgery

Answer 4

chrohns is TH1 vs TH2 mediated, and involves TNFalpha vs IL-13- also defective T cell apoptosis vs normal apoptosis

.affects all layers+ any part of gut vs only mucosa and rectum

.patchy vs continuous

.fistulae (hole in gut) vs nont

.surgery doesn’t often cure vs can cure

Question 5

clinical features- local and systemic

Answer 5

abdominal fain, diarrhoea/bloody faeces, mouth ulcers

.can also be systemic- fever, anemia, skin rashes, weight loss

Question 6

supportive therapies and hwo for

Answer 6

fluids/electrolyes, blood and nutrition- for acutely sick pl

Question 7

treatment NAD prevention of remission of disease

Answer 7

glucocorticoids, aminosalicylates, immunsurpressants

Question 8

treatment of severe/ possibly curable cases

Answer 8

manipulating microbiome and biological therapies

Question 9

aminosalicylates- examples

Answer 9

mesalazine (5-ASA) and olsalazine

Question 10

pharmacokinetics of these drgs- metabolism+ absorption

Answer 10

often metabolised in colon to active drug, and absorbed in colon

Question 11

mechanism of aminosalicylates

Answer 11

anti-inflammatory, reduces MAPK= less pro-inflammatory cytokines eg TNF alpha, and reduces COX2= less prostaglandins

Question 12

how to give aminosalicylates and is it better than glucocorticoids

Answer 12

combined oral and rectal administration- better than glucocorticoids

Question 13

aminosalicylates in CD vs UC, and what given instead

Answer 13

used in UC, not very good in CD- glucocorticoids given usually for CD

Question 14

mechanism of glucocorticoids

Answer 14

anti-inflammatory- downregulates TNF-alpha and actions of T cells

Question 15

examples of glucocorticoids and which safer, and which better

Answer 15

prednisolone and budesonide- budesonide more topical (stays in gut), so less side effects (prednisolone has LOTS of side effects), but prednisolone better, so give budesonide if IBD is MILD

Question 16

azathrioprine- what converted to, and mechanism

Answer 16

converted to 6-mercaptopurine- is IMMUNOSURPRESSIVE, as leads to less T cells and antibody production+ T cell apoptosis

Question 17

what azathrioprine used for

Answer 17

crohns, not UC- not effective for acive disease, but rather preventing RELAPSE

Question 18

side effects of azathrioprines

Answer 18

side effects severe- pancreatitis, liver issues, increased risk of cancer, problems with bone marrow

Question 19

mechanism of azathrioprines with relation to side effects

Answer 19

produces 6-MeMP= toxic to liver- produces 6-TGN= bone marrow issues

Question 20

how to minimise side effects of all these drugs

Answer 20

give drugs topically eg budesonise, and gives in low doses with another drug

Question 21

how to target drug delivery

Answer 21

prevent in being broken down in eg stomach by giving it as PRODRUG, which is only broken down in colon, or broken down in a specific TIME, or broken down depending on PH

Question 22

manipulation of microbiome (enteral nutrition)- what is it, how it work, when given, problem

Answer 22

enteral nutrition- liquid diet only, gives rest to gut flora: hard to maintain: only if patient can’t taken glucocorticoids

Question 23

manipulation of microbiome (probiotics)

Answer 23

little evidence fo rboth diseases

Question 24

manipulation of microbiome- faecal microbiota replacement

Answer 24

replacing harmful microbiota with good microbioata- some evidence

Question 25

manipulation of microbiomes- antibiotics

Answer 25

rifaximin- often given in infection

Question 26

biologic therapies- example, what disease used for, what it good for

Answer 26

anti-TNF alpha antibodies ie infliximab- used for crohns, helps repair fistulae

Question 27

problems with anti-TNF

Answer 27

oten not maintained= increases risk of cancer/HF/TB

Question 28

when infliximab used

Answer 28

often combined with azothrioprine